Efficient Hydrolysis of Gluten-Derived Celiac Disease-Triggering Immunogenic Peptides by a Bacterial Serine Protease from Burkholderia gladioli

Celiac disease is an autoimmune disorder triggered by toxic peptides derived from incompletely digested glutens in the stomach. Peptidases that can digest the toxic peptides may formulate an oral enzyme therapy to improve the patients’ health condition. Bga1903 is a serine endopeptidase secreted by Burkholderia gladioli. The preproprotein of Bga1903 consists of an N-terminal signal peptide, a propeptide region, and an enzymatic domain that belongs to the S8 subfamily. Bga1903 could be secreted into the culture medium when it was expressed in E. coli. The purified Bga1903 is capable of hydrolyzing the gluten-derived toxic peptides, such as the 33- and 26-mer peptides, with the preference for the peptide bonds at the carbonyl site of glutamine (P1 position). The kinetic assay of Bga1903 toward the chromogenic substrate Z-HPQ-pNA at 37 °C, pH 7.0, suggests that the values of Km and kcat are 0.44 ± 0.1 mM and 17.8 ± 0.4 s−1, respectively. The addition of Bga1903 in the wort during the fermentation step of beer could help in making gluten-free beer. In summary, Bga1903 is usable to reduce the gluten content in processed foods and represents a good candidate for protein engineering/modification aimed to efficiently digest the gluten at the gastric condition.

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Gliadin Sequestration as a Novel Therapy for Celiac Disease: A Prospective Application for Polyphenols

International Journal of Molecular Sciences ◽

10.3390/ijms22020595 ◽

2021 ◽

Vol 22 (2) ◽

pp. 595

Author(s):

Charlene B. Van Buiten ◽

Ryan J. Elias

Keyword(s):

Immune Response ◽

Celiac Disease ◽

Gastrointestinal Symptoms ◽

Autoimmune Disorder ◽

Treatment Method ◽

Mucosal Damage ◽

Protective Effects ◽

Novel Therapy ◽

Gluten Proteins ◽

Prospective Application

Celiac disease is an autoimmune disorder characterized by a heightened immune response to gluten proteins in the diet, leading to gastrointestinal symptoms and mucosal damage localized to the small intestine. Despite its prevalence, the only treatment currently available for celiac disease is complete avoidance of gluten proteins in the diet. Ongoing clinical trials have focused on targeting the immune response or gluten proteins through methods such as immunosuppression, enhanced protein degradation and protein sequestration. Recent studies suggest that polyphenols may elicit protective effects within the celiac disease milieu by disrupting the enzymatic hydrolysis of gluten proteins, sequestering gluten proteins from recognition by critical receptors in pathogenesis and exerting anti-inflammatory effects on the system as a whole. This review highlights mechanisms by which polyphenols can protect against celiac disease, takes a critical look at recent works and outlines future applications for this potential treatment method.

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Celiac Disease

Cases on Medical Nutrition Therapy for Gastrointestinal Disorders - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-7998-3802-9.ch005 ◽

2021 ◽

pp. 93-114

Author(s):

Haalah M. Shaaker

Keyword(s):

Celiac Disease ◽

Autoimmune Disorder ◽

Nutrition Therapy ◽

Medical Nutrition Therapy ◽

Nutrient Supplements ◽

Proximal Small Intestine ◽

Packaged Foods ◽

Medical Nutrition

This chapter reveals and discusses a case involving celiac disease (CD). CD is a common, lifelong, genetically-based autoimmune disorder that causes inflammation of the proximal small intestine. This disease is triggered by eating foods containing gluten, which causes intestinal discomfort. Gluten is a protein that is found naturally in wheat, barley, and rye and is common in foods such as bread, pasta, cookies, and cakes. Many pre-packaged foods, lip balms and lipsticks, hair and skin products, toothpaste and vitamin and nutrient supplements contain gluten, although it is rarely found in medicine. The key to living with CD is to follow a gluten-free diet. This case shows the role of medical nutrition therapy in managing and preventing the undesirable symptoms of CD. Moreover, it allows dietetic professionals to assess celiac patients' conditions and provide them with relief from undesirable symptoms, while also establishing an effective follow-up plan with each patient.

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Examining core self-management skills among adolescents with celiac disease

Journal of Health Psychology ◽

10.1177/1359105320922304 ◽

2020 ◽

pp. 135910532092230

Author(s):

Sonya Meyer ◽

Sara Rosenblum

Keyword(s):

Celiac Disease ◽

Executive Function ◽

Cognitive Skills ◽

Chronic Health Condition ◽

Cross Sectional Study ◽

Health Condition ◽

Management Skills ◽

Cross Sectional ◽

Daily Food ◽

Core Self

A strict gluten-free diet is the only treatment for celiac disease, and it is especially challenging among adolescents. Participation in food-related activities and self-managing the chronic health condition involve use of cognitive skills. This cross-sectional study examined how executive functions might be associated with participation in food-related activities. Adolescents aged 12–18 years ( N = 65; Mage = 14.67) with celiac were interviewed about participation, and their parents completed an executive function questionnaire. Poorer participation significantly correlated with poorer executive abilities. Identifying executive function profiles may contribute to understanding and advancing resourceful daily functioning and participation in daily food-related activities.

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Atherosclerotic Risk Factors in Children with Celiac Disease

Gastroenterology Research and Practice ◽

10.1155/2020/6138243 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Anna Rybak ◽

Aldona Wierzbicka ◽

Piotr Socha ◽

Anna Stolarczyk ◽

Bożena Cukrowska ◽

...

Keyword(s):

Risk Factors ◽

Celiac Disease ◽

Folic Acid ◽

Lipid Profile ◽

Total Cholesterol ◽

Reference Group ◽

Autoimmune Disorder ◽

Healthy Children ◽

Positive Correlation ◽

The Impact

Introduction and Objectives. Celiac disease (CD) is a complex autoimmune disorder occurring in genetically susceptible individuals. There is limited data on the impact of gluten-free diet (GFD) on the risk of developing cardiovascular diseases. Hereby, we present our study regarding the impact of treatment with GFD on the biochemical risk factors of atherosclerosis. Material and Methods. 277 patients with CD from 7 Polish clinics were enrolled in the study (210 children treated for at least 5 years and 67 children included in the study on the day of CD diagnosis and observed for 1 year on a GFD). We obtained selected clinical data, and we assessed lipid profile, apolipoproteins (A1, B, and E), lipoprotein (a), homocysteine, as well as antioxidants (folic and uric acid), and high-sensitivity CRP (hsCRP) for all patients. The compliance to GFD was verified using anti-transglutaminase antibodies and deamidated gliadin peptide antibodies. As a reference group, the data of 95 healthy children recruited for another project was used, for which we had the results of selected parameters. Results. We found significantly lower concentrations of total cholesterol, lipoprotein LDL-C, apolipoproteins A1 and B, as well as hCRP in all children with CD. We showed decreased level (<5 ng/mL) of folic acid among 46% of children treated for >5 years. Moreover, we showed significant decrease of folic acid level already after 1 year of a GFD (12 vs. 5.6 ng/mL; p<0.001). We also found significant negative correlation of z-score body mass index (BMI) with HDL and APOA1 level (r=−0.33; p=0.015 and r=−0.28; p=0.038, respectively) and modest positive correlation of z-score BMI with atherogenic factor of total cholesterol-HDL ratio and LDL-HDL ratio (r=0.40; p=0.002 and r=0.36; p=0.006, respectively). Analysis of physical activity showed an increase in the insulin levels with inactivity (r=0.36; p=0.0025). We also found positive correlation of the sleep duration with the adiponectin level (r=0.41; p=0.011). Conclusions. In children with CD treated with a GFD, decreased level of folic acid together with increased BMI, sedentary behavior, and an improper lipid profile may predispose them to atherosclerosis in the long run. This data suggests the need of further studies to determine the need for metabolic cardiovascular risk screening in children with CD.

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P.06.13 FECAL GLUTEN IMMUNOGENIC PEPTIDES: COULD BE CONSIDERED AS POSSIBLE MARKERS IN THE EVALUATION OF ADHERENCE TO GLUTEN FREE DIET IN CELIAC DISEASE PATIENTS?

Digestive and Liver Disease ◽

10.1016/s1590-8658(19)30443-8 ◽

2019 ◽

Vol 51 ◽

pp. e218

Author(s):

M. Marini ◽

B. Porcelli ◽

I. Biviano ◽

A. Santini ◽

L. Terzuoli ◽

...

Keyword(s):

Celiac Disease ◽

Gluten Free Diet ◽

Gluten Free ◽

Immunogenic Peptides

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A new microbial gluten-degrading prolyl endopeptidase: Potential application in celiac disease to reduce gluten immunogenic peptides

PLoS ONE ◽

10.1371/journal.pone.0218346 ◽

2019 ◽

Vol 14 (6) ◽

pp. e0218346 ◽

Cited By ~ 3

Author(s):

María de Lourdes Moreno Amador ◽

Miguel Arévalo-Rodríguez ◽

Encarnación Mellado Durán ◽

Juan Carlos Martínez Reyes ◽

Carolina Sousa Martín

Keyword(s):

Celiac Disease ◽

Potential Application ◽

Prolyl Endopeptidase ◽

Immunogenic Peptides

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Antimicrobial Properties of a Chitosan Dextran-Based Hydrogel for Surgical Use

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05463-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 280-287 ◽

Cited By ~ 80

Author(s):

Manal A. Aziz ◽

Jaydee D. Cabral ◽

Heather J. L. Brooks ◽

Stephen C. Moratti ◽

Lyall R. Hanton

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Bacterial Species ◽

Antimicrobial Properties ◽

Sinus Surgery ◽

Peptide Bonds ◽

Content Type ◽

E Coli ◽

Transmission Electron

ABSTRACTA chitosan dextran-based (CD) hydrogel, developed for use in endoscopic sinus surgery, was tested for antimicrobial activityin vitroagainst a range of pathogenic microorganisms. The microdilution technique was used to determine minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations. In addition, the time-kill efficacy of CD hydrogel was determined for two bacterial species. Scanning and transmission electron microscopy were carried out to elucidate the antimicrobial mechanism of this compound. CD hydrogel was found to be effective againstStaphylococcus aureus,Streptococcus pyogenes,Escherichia coli, andClostridium perfringensat its surgical concentration of 50,000 mg/liter. Minimum bactericidal concentrations ranged from 2,000 to 50,000 mg/liter. Dextran aldehyde (DA) was found to be the antimicrobial component of the CD hydrogel with MBC ranging from 2,000 to 32,000 mg/liter.S. aureusappeared to be killed at a slightly faster rate thanE. coli. Candida albicansandPseudomonas aeruginosawere more resistant to CD hydrogel and DA. Scanning and transmission electron microscopy ofE. coliandS. aureusincubated with CD hydrogel and DA alone revealed morphological damage, disrupted cell walls, and loss of cytosolic contents, compatible with the proposed mode of action involving binding to cell wall proteins and disruption of peptide bonds. Motility and chemotaxis tests showedE. colito be inhibited when incubated with DA. The antibacterial activity of CD hydrogel may make it a useful postsurgical aid at other body sites, especially where there is a risk of Gram-positive infections.

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